Acta Derm Venereol 2002; 82: 241–244
MINI REVIEW
Multiple Eruptive Dermatofibromas: A Review of the Literature
SHIRO NIIYAMA1,2 , KENSEI KATSUOKA2 , RUDOLF HAPPLE1 and ROLF HOFFMANN1
1Department of Dermatology, Philipp University, Marburg, Germany and 2Department of Dermatology, Kitasato University, Kanagawa, Japan
In this review we summarize the characteristic features of
multiple eruptive dermatoŽ bromas based on an analysis
of cases in the literature. Many researchers have reported
multiple eruptive dermatoŽ bromas diagnosed using the
deŽ nition of ‘‘multiple’’ as the presence of at least 15
lesions. However, this criterion is arbitrarily chosen and
might not be entirely valid for all cases. A more precise
deŽ nition may include the eruption of several multiple
eruptive dermatoŽ bromas reported within a short period of
time. Because more than half of the patients with multiple
eruptive dermatoŽ bromas have underlying diseases, and
more than 80% of the underlying diseases are immunemediated, multiple eruptive dermatoŽ bromas could possibly be considered as a partial manifestation of an
immune-mediated disease. This underscores the possibility
of early diagnosis of immune-mediated diseases in patients
with multiple eruptive dermatoŽ bromas. Key words:
underlying diseases; immune diseases; SLE; HIV.
(Accepted March 20, 2002.)
of the body, where the number of lesions is larger.
Facial lesions are extremely rare, as is also true of cases
of ordinary DF. In some cases, MEDF occurred in
unusual areas such as the palms and soles (7), eyelids
(9) or buttocks (19) but, remarkably, none of these
cases had any associated underlying disease. In general,
MEDF arranged in a more limited area may not be
associated with any underlying diseases.
Onset of multiple eruptive dermatoŽ bromas
A typical clinical feature of MEDF is the sudden appearance of many DFs not only on the legs but also elsewhere
on the body. In addition to the number of DFs, it is
important to note the dynamic changes in some lesions
within a short period of time in contrast to the static
state usually observed in common DFs. Ammirati et al.
(29) proposed that MEDF should be deŽ ned as the
presence of 5 to 8 DFs appearing within a period of
4 months.
Acta Derm Venereol 2002; 82: 241–244.
Shiro Niiyama, Department of Dermatology, Kitasato
University, 1-15-1 Kitasato, Sagamihara-shi Kanagawa,
228-8555 Japan.
DermatoŽ broma (DF ) is a common, benign Ž brohistiocytic tumor that usually occurs on the legs. Cases of
solitary DF or occasionally a few DFs are common, but
multiple eruptive dermatoŽ bromas (MEDF ) are rarely
observed (1–34). Multiple dermatoŽ bromas were present in 106 of the 379 patients ( 28%) reviewed by Niemi
(35): 76 patients (20%) had two lesions, 29 patients
(8%) had between 3 and 10 lesions, and only one patient
(0.3%) had more than 10 lesions.
In this review we summarize the cases of MEDF
showing at least 3 DFs published in the English literature
since 1960, and describe the characteristic features of
this condition. Because of the widely accepted view that
histiocytoma is a synonym of DF (5), we used both
terms when retrieving cases from the literature.
Body distribution of multiple eruptive dermatoŽ bromas
MEDF characteristically occur in the legs, as indicated
in Table I, as do most DFs (19), regardless of the
presence or absence of underlying disease. In contrast
to ordinary DFs, however, they also occur in other parts
© 2002 Taylor & Francis. ISSN 0001-555 5
DeŽ nition of ‘‘multiple’’
Since MEDF were Ž rst reported by Baraf & Shapiro in
1970 (3), deŽ ning ‘‘multiple’’as the presence of at least
15 lesions, many researchers have reported cases of
MEDF diagnosed on this basis (4, 14, 15, 18, 25, 31,
32). However, the relevance of the number 15 is still in
question (4, 31). Out of the 39 case reports in which
the number of lesions was speciŽ ed in the literature, 20
(51%) had 15 or more DFs. However, even in those
patients with 14 or fewer DFs, new DFs could have
been in the process of proliferation. Conversely, DFs
may also disappear spontaneously (15, 22, 31), as has
occasionally been reported. Therefore, the deŽ nition of
MEDF based purely on the number of DFs may not be
entirely valid (21, 27). DeŽ ning MEDF solely on the
basis of the number of lesions may be as arbitrary as
deŽ ning the so-called sign of Leser-Trélat solely by the
number of seborrheic keratoses.
Characteristic underlying diseases associated with
MEDF
There are several reports indicating that patients with
MEDF often have various underlying diseases. From
our review, as presented in Table I, we deduce that the
incidence of MEDF is higher among patients with
underlying diseases (28/50, 56%) than among otherwise
Acta Derm Venereol 82
242
S. Niiyama et al.
Table I. A review of the patients with multiple eruptive dermatoŽ bromas
Associated condition
DermatoŽ bromas
Ref. No.
Sex/Age
Disease
Druga
No.
Locationb
1
2
2
2
3
4
4
4
4
5
5
6
7
7
7
7
8
9
10
11
12
13
14
15
15
15
16
17
18
18
19
20
21
22
22
22
23
24
25
26
27
28
29
29
29
30
31
32
33
34
F/71
F/53
M/58
F/38
F/39
F/54
F/40
M/50
F/64
F/31
F/19
M/44
M/12
M /8
F/36
F/9
F/49
F/62
M/52
F/37
M/47
M/27
M/53
F/41
F/50
F/28
M/37
M/29
M/45
F/20
F/23
F/38
F/25
F/52
F/33
F/46
M/24
M/37
F/33
M/24
F/43
M/38
M/36
M/40
M/38
F/18
F/51
M/45
M/13
F/48
Hydronephrosis
–
–
–
–
–
–
–
–
SLE
SLE
–
–
–
–
–
SLE
–
–
SLE
–
–
Myasthenia gravis
SLE, Sjögren syndrome
SLE
SLE
–
Atopic dermatitis
Pemphigus vulgaris
SLE
–
SLE
Pregnancy
SLE
–
SLE, Sjögren syndrome
HIV, hepatitis B
HIV
SLE, HIV
HIV, psoriasis
Sarcoidosis
HIV
HIV
HIV
HIV
–
Mycosis fungoides, interstitial pneumonia
HIV
–
SLE
–
–
–
–
–
–
–
–
–
Steroid, Aza
Steroid
–
–
–
–
–
ND
–
–
Steroid
–
–
Steroid, Cyc
Steroid
ND
Steroid
–
Steroid (topical )
Steroid
Steroid
–
Steroid
–
Steroid
–
Steroid, Cyc
DHIV, INFa
DHIV
Steroid, DHIV
DHIV, Steroid, UVB
Steroid, ACTH
ND
DHIV
DHIV
DHIV
–
PUVA, UVB, Steroid
DHIV
–
Steroid
Over 30
85
2000
> 1000
61
90
16
23
12
15
Several
ND
9
Multiple
Multiple
6
Multiple
Multiple
ND
6
10
> 100
50–70
120
27
18
ND
Many dozens
23
4
ND
20
9
13
11
10
11
7
15
8
20
ND
7
8
5
ND
14
Multiple
ND
About 20
LL
T, UL, LL
T, UL, LL
F, T, UL, LL
T, UL, LL
T, UL, LL
T, UL, LL
T, UL, LL
UL, LL
UL, LL
T, LL
T, LL
Palm
Hand
Palm
Palm, sole
LL
Eyelid
F, T, UL, LL
T, UL, LL
T, UL, LL
T, UU, LL
T, UL, LL
T, UL, LL
T, UL, LL
UL, LL
LL
F, T, UL, LL
LL
T, LL
Buttock
UL, LL
T, UL, LL
T, UL
T, UL, LL22
ND
T, LL
T, LL
T, UL, LL
T, UL, LL
T, LL
UL, LL
T, UL, LL
UL, LL
T, UL, LL
T, UL, LL
LL
LL
T, LL
LL
aAza: azathioprine; Cyc: cyclophosphamide; DHIV: drugs for HIV infection; ND: not described.
bF: face; T: trunk; UL: upper limb; LL: lower limb; SLE: systemic lupus erythematosus; ACTH: adrenocorticotrope hormone.
healthy persons (22/50, 44%). MEDF are usually associated with systemic lupus erythematosus (SLE ) (13/28,
46%) or HIV infection (9/28, 32%), followed by other
immune-mediated diseases, such as myasthenia gravis
and pemphigus vulgaris. Although in some previous
studies it is suggested that diabetes mellitus (1), obesity
Acta Derm Venereol 82
( 4), hyperlipidemia (4), and hypertension (4 ) might also
be frequently encountered in these patients, a correlation
between MEDF and the presence of these diseases,
which have high rates of prevalence in the general
population, seems to be questionable.
According to our reassessment of published reports,
Multiple eruptive dermatoŽ bromas
the male:female ratio of patients with MEDF is 0.72:1,
indicating a slight female predominance. When these
patients are classiŽ ed in terms of the presence or absence
of underlying diseases (n = 22), the male:female ratio is
0.83:1 in patients with no underlying disease (n = 28),
whereas it is 0.65:1 in those who had underlying diseases.
However, this may be because SLE accounted for about
half of the cases with underlying diseases, and it is well
known that SLE occurs predominantly in women.
Because MEDF were associated with other diseases
in more than half of the reviewed cases, and more than
80% of the underlying diseases were immune mediated,
MEDF could be considered in part as a manifestation
of an immune-mediated disease. In recent years, the
development of MEDF has been regarded as a dermal
manifestation of HIV infection (32). In some cases, the
onset of MEDF preceded the onset and diagnosis of the
associated immune-mediated disease (8, 15, 23). This
underscores the possibility of early diagnosis of immunemediated diseases in patients recognized as having
MEDF.
It is of particular interest to clarify whether the
symptoms of MEDF show any changes along with
aggravation of the underlying disease, or, in other words,
whether changes in the symptoms of MEDF can predict
changes in the severity of the underlying disease. Only
two cases were reported in which the two conditions
showed parallel aggravation in severity (8, 31). Usually,
however, there seemed to be no correlation between the
severity of the underlying disease and the symptoms
of MEDF.
Some patients with immune-mediated diseases
developed MEDF after intake of immunosuppressive
drugs or after an increase in the dose of the medication,
suggesting a causal relationship between the medication
and the development of MEDF (5, 11, 14, 15, 23, 26).
Based on this data, the possibility of the occurrence of
immunomodulatory, drug-induced MEDF has been discussed. However, it should be noted that the commencement, or increase in the dose of medication is usually
prompted by aggravation of the underlying disease, and
that it is therefore impossible to determine whether the
development of MEDF is induced by aggravation of
the underlying disease or by the use of drugs.
Etiology of multiple eruptive dermatoŽ bromas
The etiology of DF is unclear. It may represent a
neoplastic process or a persistent in ammatory proliferation of Ž broblasts secondary to trauma (such as an
insect bite) (36). Recently, it was proposed that DF
represents an abortive immunoreactive process mediated
by dermal dendritic cells (37). According to this hypothesis, the development of MEDF can be triggered by
the inhibition of down-regulatory T cells in immunodeŽ ciency states. The increased incidence of MEDF in
patients with immune-mediated diseases and the rela-
243
tionship with immunosuppressive treatment strongly
suggest that immune mechanisms may play a role in the
pathogenesis of DF.
Conclusion
For the diagnosis of MEDF, it is important to note the
dynamic changes in the form of an outbreak of lesions
within a short period of time.
MEDF may develop in patients with immunemediated diseases. Hence, the possibility of an underlying immune-mediated disease should be borne in mind
when encountering patients with MEDF.
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